Quantitative reconstruction of cardiac electromechanics in human myocardium: Assembly of electrophysiologic and tension generation models

Reconstruction of Electromechanics in Cardiomyocytes. Introduction: Myocytes from normal and failing myocardium show significant differences in electromechanical behavior. Mathematical modeling of the behavior provides insights into the underlying physiologic and pathophysiologic mechanisms. Electromechanical models of cardiomyocytes exist for various species, but models of human myocytes are lacking. Methods and Results: A mathematical model of electromechanics in normal and failing cardiac myocytes in humans was created by assembly and adaptation of parameters of an electrophysiologic model at the level of single cells and a force development model at the level of the sarcomere. The adaptation was performed using data from recent studies of ventricular myocytes and myocardium. The model was applied to quantitatively reconstruct measurement data from different experimental studies of normal and failing myocardium. Several simulations were performed to quantify the transmembrane voltage V-m, intracellular concentration of calcium[Ca2+](i), the [Ca2+](i)-force relationship, and force transients. Furthermore, frequency dependencies and restitution of action voltage duration to 90% recovery APD(90), peak [Ca2+](i), duration to 50% force recovery FD50, and peak force were determined. Conclusion: The presented mathematical model was capable of quantitatively reconstructing data obtained from different studies of electrophysiology and force development in normal and failing myocardium of humans. In future work, the model can serve as a component for studying macroscopic mechanisms of excitation propagation, metabolism, and electromechanics in human myocardium.